Chapter 5 (Chromosomes)

Front 1

Eukaryotes

Back 1

Many chromosomes;

Linear chromosomes;

made of chromatin, a nucleoprotein (DNA coiled around histone proteins) ;

found in a nucleus;

copies chromosomes, then the cell grows,then goes through mitosis to organize chromosomes in two equal groups.

Hint 1

Front 2

Chromosomes are too _____ to be seen, except with an _______microscope

Back 2

thin

electron when

Front 3

when the cell is ______, they got ______ & ______ so they can be seen with a light microscope

Back 3

dividing

shorter & fatter

Front 4

Packed form of DNA

Back 4

chromosomes

Front 5

DNA normally exists in a __________ form in the _________

Back 5

non-condensed form

cell nucleus

Front 6

DNA normally exists in a __________ form in the _________

Back 6

non-condensed form

cell nucleus

Front 7

chromosomes condenses during ________

Back 7

cell replication

Front 8

Human cells contain ___ chromosomes, which are in pairs

Back 8

46

Front 9

each chromosomes contains ____________molecule of DNA

Back 9

one very long molecule

Hint 9

Front 10

DNA molecule carries a ____ that _____ the cell about which kind of _____ it should make.

Back 10

a code

instructs

protein

Front 11

each chromosomes carries instructions for making __________

Back 11

different proteins

Front 12

Gene

Back 12

Each chromosome is made up of a large number of genes coding for the formation of different proteins which give us our characteristics.

Hint 12

Front 13

Gene

Back 13

The gene responsible for a particular characteristic is always on the same relative position on the chromosome.

Front 14

Alleles

Back 14

When the chromosomes are in pairs, there may be a different form (allele) of the gene on each chromosome.

Hint 14

Front 15

Prokaryotes

Back 15

single chromosomes plus plasmids ;

Circular chromosomes;

made only of DNA;

found in cytoplasm;

copies the chromosomes and divides immediately afterwards.

Hint 15

Front 16

Eukaryotes

Back 16

Many chromosomes;

Linear chromosomes;

made of chromatin, a nucleoprotein (DNA coiled around histone proteins) ;

found in a nucleus;

copies chromosomes, then the cell grows,then goes through mitosis to organize chromosomes in two equal groups.

Hint 16

Front 17

pairing

Back 17

Except for certain cells (for example, sperm and egg cells or red blood cells), the nucleus of every human cell contains 23 pairs of chromosomes, for a total of 46 chromosomes.

Front 18

DNA molecule carries a ____ that _____ the cell about which kind of _____ it should make.

Back 18

a code

instructs

protein

Front 19

pairing

Back 19

Because each member of a pair of nonsex chromosomes contains one of each corresponding gene, there is in a sense a backup for the genes on those chromosomes.

Front 20

pairing

Back 20

the 23rd pair is the sex chromosomes (X andY)

Front 21

Sex chromosomes

Back 21

The pair of sex chromosomes determines whether a fetus becomes male or female. Males have one X and one Y chromosome. - male’s X comes from his mother and Y comes from his father

Females have two X chromosomes, one from the mother and one from the father.

In certain ways, sex chromosomes function differently than nonsex chromosomes.

Front 22

genes on the X chromosomes are referred to as _______, or X-linked genes.

Back 22

sex-linked, or X-linked genes.

Front 23

each chromosomes carries instructions for making __________

Back 23

different proteins

Front 24

Gene

Back 24

Each chromosome is made up of a large number of genes coding for the formation of different proteins which give us our characteristics.

Front 25

Gene

Back 25

The gene responsible for a particular characteristic is always on the same relative position on the chromosome.

Front 26

Alleles

Back 26

When the chromosomes are in pairs, there may be a different form (allele) of the gene on each chromosome.

Front 27

Prokaryotes

Back 27

single chromosomes plus plasmids ;

Circular chromosomes;

made only of DNA;

found in cytoplasm;

copies the chromosomes and divides immediately afterwards.

Front 28

Eukaryotes

Back 28

Many chromosomes;

Linear chromosomes;

made of chromatin, a nucleoprotein (DNA coiled around histone proteins) ;

found in a nucleus;

copies chromosomes, then the cell grows,then goes through mitosis to organize chromosomes in two equal groups.

Front 29

pairing

Back 29

Except for certain cells (for example, sperm and egg cells or red blood cells), the nucleus of every human cell contains 23 pairs of chromosomes, for a total of 46 chromosomes.

Front 30

pairing

Back 30

Normally, each pair consists of one chromosome from the mother and one from the father.

Front 31

pairing

Back 31

There are 22 pairs of nonsex (autosomal) chromosomes and one pair of sex chromosomes.

Paired nonsex chromosomes are, for practical purposes, identical in size, shape, position and number of genes,

Front 32

X inactivation

Back 32

in females, most of the genes on one of the two X chromosomes are turned off through a process called X inactivation (except in the eggs in the ovaries).

X inactivation occurs early in the life of the fetus.

Front 33

The chromosome condenses …. and then ______ happens.

Back 33

mitosis

Front 34

During cell division centromeres are region of the chromosome where the _________ attaches.

Back 34

kinetochore

Front 35

kinetochore

Back 35

a protein machine that mediates the following events:

1) The duplicated chromosomes are aligned along a plane in the middle of the cell

2) Chromosomes are then split into their individual chromatid copies

3) One of each copy is dragged to the two poles of the cell. This is mediated by the kinetochore attached to the centromere,

so the centromere is the basis for segregation, and the rest of the chromosome just follows the lead of the centromere.

Front 36

Aneuploid

Back 36

cells with the wrong number of chromosomes

Commonly seen in cancers

Front 37

structure of centromeres

Back 37

The placement of centromeres relative to the length of the chromosome is different for each chromosome.

Centromeres can be in the center of the chromosome (as the name would suggest), or towards an end.

Centromeres consist of some defined sequence elements, but are mostly less well defined repetitive sequence. A minimal centromere in yeast can be defined that is 120 base pairs long.

Front 38

In multicellular eukaryotes, centromeres typically occupy several ______ _______base pairs, and include the alpha satellite repetitive sequence.

Back 38

hundred thousand

Front 39

Although the exact DNA sequence of a centromere is _______ _______ from one chromosome to another, chromosome centromeres nevertheless are functionally equivalent.

They are readily _________ between chromosomes;

e.g. the X chromosome centromere could be swapped with the Y chromosome centromere with no ill effect.

Back 39

fairly variable

interchangeable

Front 40

Centromeres maintain a _________, _________ structure throughout the life of the cell.

Nucleosomes in centromeres possess the histone H3 variant CENP-A, which helps direct kinetochore attachement.

Back 40

condensed

heterochromatin

Front 41

Telomeres Structure and function

Back 41

A Linear chromosome means it has ends, which presents two major problems.

1) A short amount of sequence at the end of the chromosome is left un-replicated after every round of replication. If this proceeded indefinitely, genes near the ends of the chromosome would get deleted.

2) DNA ends are a problem for cells; they are Sensitive to degradation, and are seen by the cell as a form of DNA damage. If seen as damage, chromosome ends could either trigger a "repair" reaction, where the ends of two chromosomes are fused together or the chromosome end could trigger cell death by "checkpoint pathways". Fusion of chromosomes will mean that they can't segregate properly during mitosis.

Front 42

Telomeres Structure and function

Back 42

the telomere is a short repeated-sequence; the number and sequence of repeats varies between organisms (there are 500 to 2000 repeats of the TTAGGG sequence in each human telomere).

Front 43

X inactivation

Back 43

the absence of one X chromosomes usually results in relatively minor abnormalities

(Such as Turner syndrome)

Front 44

telomerase

Back 44

specific enzyme that several telomeric repeats are added every round of replication

Is like a standard DNA polymerase in that it adds new DNA to the 3’end of a DNA chain

Front 45

telomerase does not use a DNA template to direct synthesis; it uses an intrinsic _____ component of the enzyme to act as the template strand

Back 45

RNA

Front 46

The RNA component has, as part of its sequence, the complementary sequence to 5’TTAGGG3’ so it can ______ _______ of TTAGGG repeats only

Back 46

direct synthesis

Front 47

Loops

Back 47

Telomeres Form loops. A single stranded tail at the end of the telomere loops back and inserts itself into a region of telomere double helix.

This is termed the "loop", and was discovered in

1999 by Dr. Jack Griffith (UNC) and Titia de Lange. Formation of the loop, and protection of the branch point, is mediated by the TRF-2 protein (Telomere Repeat binding Factor-2).

This loop essentially hides the chromosome end, and means the end of the chromosome isresistant to degradation or "repair"

Front 48

Telomeres, aging, and cancer

Back 48

There is a link between the potential of cells to regularly divide (proliferative capacity) and the length of their telomeres. Cells with short telomere; have limited proliferative capacity, cells with long telomeres have much greater proliferative capacity,

This leads to the idea that telomeres are a "clock" that helps define proliferative capacity.

Front 49

Senescence

Back 49

After a limited number of divisions (the number varies according to cell type) the telomeres have shortened to a point where a signal is sent that stops the cells from dividing further

Front 50

cellular senescence

Back 50

a significant component of aging

Front 51

Cancer-causing mutations can force such a differentiated cell to ______ _____ again; however, the telomeres continue to _____. These transformed cells will eventually reach "crisis", a point at which the telomere becomes too short to permit cell _____.

Back 51

start dividing

shorten

survival

Front 52

Although most cells are killed at this point, some survive to cause cancer because they have "_______" to re-express telomerase, and their telomeres ___ _______ continue to shorten.

Back 52

“learned”

no longer

Front 53

Packaging DNA into chromosomes: chromatin

Back 53

The linear length of the human genome is about two meters &, and needs to fit in a space that is 6 microns in diameter

(this is like having a 100 kilometer long spaghetti noodle on your dinner.plate).

Front 54

missing an X chromosomes is far less harmful than missing a _________ chromosomes

Back 54

Nonsex

Front 55

Mitochondrial chromosomes

Back 55

Mitochondria are tiny structures inside cells that synthesize molecules used for energy.

Unlikeother structures inside cells, each mitochondrion contains its own circular chromosome.

This chromosome contains DNA (mitochondrial DNA) that codes for some, but not all, of the proteins that make up that mitochondrion.

Front 56

Mitochondrial DNA usually comes only from the person’s _______

Back 56

Mother

Because when an egg is fertilized, only mitochondria from egg become part of the developing embryo

Front 57

Centromeres and Telomeres

Back 57

three minimal requirements for proper maintenance of chromosomes in cells.

1) A centromere, to mediate segregatión during cell division.

2) A telomere, to protect chromosome ends.

3) Origin (s) of replication.

Centromeres and Telomeres are both repetitive DNA elements that clearly can't be called "junk" DNA.

Front 58

Centromeres

Back 58

Function:

Immediately before cell division, replication generates two copies of each chromosome

Front 59

Chromatid

Back 59

Each copy is termed a “chromatid” until copies are segregated into different cells.

Front 60

Highly organized segregation of chromatids during the mitosis phase of cell division

Back 60

when the cell divides into two daughter cells, one maternal set and one paternal set of chromosomes

Front 61

Centromere

Back 61

specific region where the chromatids are joined together along the length of the chromosomes

Front 62

There is an obvious "compaction" problem. Moreover, an ________ DNA molecule the length of a chromosome is certain to incur frequent breakage and entanglement unless organized into compact, discrete, structurally supported packets.

Back 62

unsupported

Front 63

Chromatin remodeling

Back 63

Remodeling complexes typically use the energy from ATP hydrolysis to perform remodeling. Remodeling complexes are also important in assembly of nucleosomes de novo on recently replicated DNA.

Chromatin state is altered, and remodeling facilitated or inhibited, by covalent modification of histones. These modification may act partly by loosening association of DNA with nucleosomes,because the modifications often neutralize positive charges in histone tails so the negatively charged DNA backbone no longer sticks to nucleosomes quite as tightly.

Front 64

Chromatin remodeling

Back 64

remodeling complexes often have histone modifying enzymes: histone acetylasès and deacetylases, histone methylases, and histone kinases.

Acetylation and methylation of histones are critical events both for assembly of new nucleosomes after DNA replication, as well as regulating transcription. Phosphorylation is important for chromosome condensation prior to cell division. Recently, histone phosphorylation has also been observed localized to regions of DNA damage.

Front 65

Histone variants and chromatin structure

Back 65

The histone H3 variant CENP.A helps mediate attachment of the kinetichore to centromeres.

Regions of nucleosomes where normal H2A is substituted with the H2A variant H2AZ is typically stably heterochromatic

Front 66

:)

Back 66

:)

Front 67

The nucleosome

Back 67

The basic unit of eukaryotic chromatin structure is the nucleosome.

This consists of a core octamer containing two copies each of four Histone proteins: two each of H2A, H2B, H3 and H4.

All histones are compact globular proteins with an extended tail rich in basic amino acids/positive charges

Front 68

The nucleosome

Back 68

The positive charge of the histone interacts with the negative charge of the DNA phosphate backbone.

DNA is wrapped around the octamer slightly more than twice, about 70 bp/turn, so

about 145 p of DNA wraps around each octamer. The nucleosome core particle (octamer+DNA) is about 10 nm wide

Front 69

Higher order chromatin structure

Back 69

Higher order organization (spacing and packing of adjacent nucleosomes) varies from gene to gene, and over the life of the cell.

Packing of adjacent nucleosomes is usually mediated at least in part by histone H1 (linker histone).

Adjacent nucleosomes are often packed into higher order 30 nm wide fibers, a helical arrangementof stacked adjacent nucleosomes in a structure of approximately 6 nucleosomes/turn

Front 70

30 nm fibers can be further organized into ___-___kilobase pair loops; the base of these loops are attached to protein scaffotds.

These loops are packed together into a _____,_____ immediately prior to cell division

Back 70

20-100

regular, tightly condensed structure

Front 71

Chromatin and DNA metabolism.

Back 71

The organization of DNA into nucleosomes and higher order chromatin solves the compaction problem, but raises another issue.

The DNA is less accessible, and thus presents a barrier to replication and transcription.

Cells therefore dynamically regulate chromatin state, condensing chromosomes for easier segregation during cell division, then stretching certain parts of the chromosome back out after cell division for transcription and replication.

Front 72

Heterochromatin and Euchromatin

Back 72

Immediately prior to cell division chromosomes are condensed into tightly packed rod-like structures, visible by standard microscopy.

After cell division is completed chromosomes are de-condensed, with regions that have actively transcribed genes reverting to a state with very loosely organized chromatin (“euchromatin").

Front 73

Heterochromatin and Euchromatin

Back 73

The extreme example of this is the heavily transcribed ribosomal RNA genes in dividing cells, which are likely almost free of nucleosomes. "Silent" regions, or heterochromatin, largely retain a highly condensed structure throughout the life of the

cell.

Front 74

Heterochromatin and Euchromatin

Back 74

Heterochromatin is found in areas of the chromosome that aren't transcriptionally active.

This often includes repetitive sequences (and in particular, centromeres and telomeres) regions near the ends of the chromosome ("sub-telomeric regions"), as well as genes not necessary for a particular cell type.

Front 75

Chromatin remodeling

Back 75

A large part of regulation of chromatin state occurs at the level of the nucleosome, by altering how tightly the octamer associates with DNA, as well as how tightly adjacent nucleosomes associate with each other.

The ability to adjust nucleosome positioning in chromatin, is termed

"remodeling".